Slack / Private Message Drop — page 394

*Discussion* The generation of insertions or deletions (indels) in or near the furin cleavage site is a frequent occurrence during coronavirus evolution (Gallaher and Garry, 2020). Passage of SARS-CoV-2 in Vero cells can result in deletion of either the furin cleavage site or a sequence immediately adjacent to it [ref]. Deletions in the spike genes of recent emerging SARS-CoV-2 variants occur preferentially in mutational hotspots that have generated insertions during embecovirus evolution. Another insertion adds amino acid E484 that is subject to further mutation during extended human-to-human passage, and which may impart enhanced fitness and/or immune escape. A caveat of the current analysis is that the amino acid alignments are not intended to precisely represent the underlying nucleotide alignments. A previous analysis suggested that the insertion generating the furin cleavage site in SARS-CoV-2 spike is out-of-frame. The molecular mechanism(s) that generated the insertions present in SASR-CoV-2 spike cannot be determined by sequence analysis. Although coronaviruses have a proof-reading apparatus, their genomes remain subject to recombination as well as copy-choice transcriptional errors [refs]. *Conclusions* It will be important to elucidate genomic features that favor indel formation and to define molecular processes occuring during coronavirus genome replication that produce indels. [2021-01-12 21:25:41] [Kristian Andersen] Bob - you and technology... :face_with_rolling_eyes: [2021-01-12 21:27:03] [Kristian Andersen] Alright... https://docs.google.com/document/d/1UMQokOz_gDqE0s9keyI7ES8bC7-55EOFuA4UiznEP08/edit?usp=sharing [2021-01-12 21:27:14] [Kristian Andersen] Welcome to 2021 - it's awesome :wink: [2021-01-12 21:27:37] [Robert Garry] I know - :rolling_on_the_floor_laughing: [2021-01-12 21:27:53] [Robert Garry] Thanks [2021-01-12 21:28:53] [Kristian Andersen] I only know one person who's worse than you :computer: - Eric Topol. Mr. Technology himself... [2021-01-12 21:44:06] [Robert Garry] Yes indeed the new pangos are important. When the Cambobat CoV confirming RaTG13 comes --- also very important. Speaking of Pangos/RatG13 the more I look at the SC2/RatG13 alignment the more I realize Boni/Rambaut were totally spot on, No need to evoke Pango recombination to generate the RBD of SC2. Can get to SC2 spike pretty easily from a RatG13 related SC2 progenitor. [2021-01-12 23:08:35] [Eddie Holmes] Thanks for the draft Bob, I'll take a look as soon as I can. Great this is moving. Cambobat CoV is also on it's way I understand. Looking forward to at least two :middle_finger::middle_finger:to the tinfoil hats. I am SO looking forward to that.